Non-vascular alterations and functional impairment persist after Anti-VEGF therapy in Oxygen Induced Retinopathy (OIR) mouse model

VALERIA ERIKA LORENC; DIEGO OMAR CROCI RUSSO; MARIA CECILIA SANCHEZ; PAULA SUBIRADA; MAGALI EVELIN RIDANO; JOSE D LUNA PINTO; MARIA CONSTANZA PAZ; GABRIEL ADRIÁN RABINOVICH

Seattle

Congreso; Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) 2016; 2016

The Association for Research in Vision and Ophthalmology

Purpose : Neovascular retinopathies are leading causes of irreversible blindness but the successful treatment remains an unmet medical need. Although Vascular Endothelial Growth Factor (VEGF) inhibitors have been established as the mainstay of current treatment, it is unclear why many patients do not improve after therapy. Animal models such as OIR have been developed in order to study these diseases in which hypoxia induces formation of abnormal neovessels (NV) as well as neuronal cell death causing retinal impairment. We hypothesized that although Anti-VEGF therapy reduces the NV do not improve associated non-vascular alterations in these retinopathies.Methods : C57BL/6 mice (OIR, N=33) were exposed to 75% O2 from postnatal day 7 (P7) to P12, after which they were brought to room air for additional five (P17) or nine days (P26). Age-matched mice maintained in room air (RA, N=15) were used as control. Some OIR mice were intraocular administered at P12 with 1,25 µg of Anti-VEGF (N=9) or vehicle (N=9). At P12, P17 and P26 mice were sacrificed and protein expression in their retinas was analyzed by Western blots. TUNEL assay and vascular staining with GSA isolectin B4 conjugated to Alexa 488 were performed. Retinal function was analyzed by electroretinogram (ERG). GraphPad Prism program was used for statistical analysis according to the experimental data.Results : VEGF expression was significantly increased in P17 OIR compared to RA (p